We have produced severe Vitamin B12 deficiency in rhesus monkeys by feeding them a defined experimental diet under controlled conditions, and have sustained the state of deficiency for long enough periods to produce changes in the spinal cord and optic nerves of these animals that are indistinguishable from those of human subacute combined degeneration (SCD). It is proposed to continue these studies (1) pursuing to completion the light and electron microscopic observations already begun (2) expanding these observations to new monkeys with particular emphasis on the early ultrastructural changes in the optic nerve and retina (3) utilizing special techniques (electron microprobe and scanning electron microscopy) for the study of the myelin alterations and (4) examining the correlation between clinical, histological and ultrastructural abnormalities and biochemical and enzymatic alterations that have been described for Vitamin B12 deficiency.